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Metabolic surgery for treating type 2 diabetes mellitus: Now supported by the world's leading diabetes organizations

July 1, 2017 | Cleveland Clinic Journal of Medicine
Philip R. Schauer, MD ; Zubaidah Nor Hanipah, MD ; Francesco Rubino, MD
Author and Disclosure Information

Philip R. Schauer, MD
Director, Bariatric and Metabolic Institute, Cleveland Clinic

Zubaidah Nor Hanipah, MD
Bariatric and Metabolic Institute, Cleveland Clinic; Department of Surgery, Faculty of Medicine and Health Sciences, University Putra Malaysia, Selangor, Malaysia

Francesco Rubino, MD
Department of Metabolic and Bariatric Surgery, Diabetes and Nutrition Science Division, King’s College London, UK

Correspondence: Philip Schauer, MD, Director, Bariatric and Metabolic Institute, M61, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; schauep@ccf.org

Dr. Schauer reported research grant support from Ethicon, Medtronic, and Pacira Pharmaceuticals; consulting fees from The Medicines Company, AMAG Pharmaceuticals, GI Dynamics, and Neurotronics; honoraria for speaking from Novo Nordisk; and ownership interest in SE HQC LLC. Dr. Nor Hanipah reported no financial interests or relationships that pose a potential conflict of interest with this article. Dr. Rubino reported research grant support from NIMR (UK Gov) and Ethicon; consulting fees from Fractyl and GI Dynamics; and honoraria for speaking from Medtronic and Ethicon.

ABSTRACT

The term metabolic surgery describes bariatric surgical procedures used primarily to treat type 2 diabetes and related metabolic conditions. Originally, bariatric surgery was used as an alternative weight-loss therapy for patients with severe obesity, but clinical data revealed its metabolic benefits in patients with type 2 diabetes. Metabolic surgery is more effective than lifestyle or medical management in achieving glycemic control, sustained weight loss, and reducing diabetes comorbidities. Perioperative adverse events are similar to other gastrointestinal surgeries. New guidelines for type 2 diabetes expand use of metabolic surgery to patients with a lower body mass index.

KEY POINTS

  • Randomized clinical trials have shown that metabolic surgery is statistically superior to medical treatment in achieving targeted glycemic levels along with improvements in weight loss, remission of metabolic syndrome, reduction in medications, and improvements in lipid levels.
  • The safety of metabolic and bariatric surgery has significantly improved with the advent of laparoscopic surgery, resulting in complication profiles similar to those of cholecystectomy and appendectomy.
  • Metabolic surgery is now recommended as standard treatment option for type 2 diabetes in patients with body mass index levels as low as 30 kg/m2.

METABOLIC SURGERY OUTCOMES

Weight loss

Long-term reduction of excess body fat is a major goal of metabolic and bariatric surgery. Weight loss is usually expressed as either the percent of weight loss or the percent of excess weight loss (ie, weight loss above ideal weight). A meta-analysis of mostly short-term weight-loss outcomes (ie, < 5 years) from more than 22,000 procedures found an overall mean excess weight loss of 47.5% for patients who underwent LAGB, 61.6% for RYGB, 68.2% for vertical-banded gastroplasty, and 70.1% for BPD-DS.16 Vertical-banded gastroplasty differs from LAGB in that both a band and staples are used to create a small stomach pouch. Excess weight loss for SG generally averages 50% to 55%, which is intermediate between LAGB and RYGB.17,18

The Swedish Obese Subjects study (N = 4,047), a prospective study of bariatric surgery vs nonsurgical weight management of severely obese patients (BMI > 34), is the largest weight-loss study with the longest follow-up.19 At 20 years, the mean weight loss was 26% for gastric bypass, 18% for vertical-banded gastroplasty, 13% for gastric banding, and 1% for controls. A 10-year study in 1,787 severely obese patients (BMI ≥ 35) who underwent RYGB had 21% more weight loss from their baseline weight than the nonsurgical match.20 At 4-year follow-up in 2,410 patients, there were significant variations in weight loss depending on the procedure: 27.5% for RYGB, 17.8% for SG, and 10.6% in LAGB. Between 2% and 31% regained weight back to baseline: 30.5% for LAGB, 14.6% for SG, and 2.5% for RYGB.20 In contrast, long-term medical (nonsurgical) weight loss rarely exceeds 5%, even with intensive lifestyle intervention.21

Diabetes remission, cardiovascular risk factors, glycemic control

A meta-analysis of 19 mostly observational studies (N = 4,070 patients) reported an overall type 2 DM remission rate of 78% after bariatric surgery with 1 to 3 years of follow-up.22 Resolution or remission was typically defined as becoming “nondiabetic” with normal HbA1c without medications. In the Swedish Obese Subjects study, the remission rate was 72% at 2 years and 36% at 10 years compared with 21% and 13%, respectively, for the nonsurgical controls (P < .001).23 Bariatric surgery was also markedly more effective than nonsurgical treatment in preventing type 2 DM, with a relative risk reduction of 78%.

A systematic review published in 2012 evaluated long-term cardiovascular risk reduction after bariatric surgery in 73 studies and 19,543 patients.24 At a mean follow-up of 57.8 months, the average excess weight loss for all procedures was 54% and rates of remission or improvement were 63% for hypertension, 73% for type 2 DM, and 65% for hyperlipidemia. Results from 12 cohort-matched, nonrandomized studies comparing bariatric surgery vs nonsurgical controls suggest that improvements in surrogate disease markers such as HbA1c, blood pressure, lipids, and body weight after surgery translate to reduced macrovascular and microvascular events and death.25 One of these studies involving male veterans who were mostly at high cardiovascular risk reported a 42% reduction in mortality at 10 years compared with medical therapy.26

In the Swedish Obese Subjects study, the mortality rate from cardiovascular disease in the bariatric surgical group was lower than for control patients (adjusted hazard ratio, 0.47; P = .002) despite a greater prevalence of smoking and higher baseline weights and blood pressures in the surgical cohort.19 For patients with type 2 DM in this study, surgery was associated with a 50% reduction in microvascular complications.27 After 15 years of follow-up, the cumulative incidence of microvascular complications was 41.8 per 1,000 person-years for control patients and 20.6 per 1,000 person-years in the surgery group (hazard ratio, 0.44; P < .001).

These observational, nonrandomized study data suggest that in patients with type 2 DM, bariatric surgery is significantly better than medical management alone in improving glycemic control, reducing cardiovascular risk factors, and lowering long-term morbidity and mortality associated with type 2 DM.

METABOLIC SURGERY: CLINICAL TRIALS

During the past 10 years, 12 randomized controlled trials (RCTs) have compared metabolic surgery vs medical treatment for type 2 DM (Table 1).28–44 All the trials included obese patients with type 2 DM (N = 874; range 38–150 patients per study) with follow-up from 6 months to 5 years. Surgeries were RYGB (9 studies), LAGB (5 studies), SG (2 studies), and BPD-DS (1 study); some studies had multiple surgery types. The severity of type 2 DM varied significantly from mild (mean HbA1c 7.7%, < 2-year onset, no insulin)28 to advanced (mean HbA1c 9.3%, duration 8.3 years, 48% on insulin).29 The BMI ranged from 25 to 53 kg/m2, with 11 of 12 studies including patients with BMI less than 35 kg/m2. Demographics of age, sex, and ethnic background were similar, although 3 studies33–35,44 included a significant number of Asian patients. For most studies, the primary end point was the success rate of reaching remission, defined as an HbA1c target at or below 6.0% to 6.5% without a need for diabetes medications.

Collectively, these RCTs showed that surgery was significantly superior to medical treatment in reaching the designated glycemic target (P < .05 for all). The one exception showed that diabetes remission for LAGB vs medical treatment was 33% and 23%, respectively.41 This result might be due to patients in this study having advanced type 2 DM (HbA1c 8.2% ± 1.2%, with 40% on insulin), and they likely had reduced beta-cell function. Overall, surgery decreased HbA1c by 2% to 3.5%, whereas medical treatment lowered it by only 1% to 1.5%. Most of these studies also showed superiority of surgery over medical treatment in achieving secondary end points such as weight loss, remission of metabolic syndrome, reduction in diabetes and cardiovascular medications, and improvement in triglycerides, lipids, and quality of life. Results were mixed in terms of improvements in systolic and diastolic blood pressure or low-density lipoproteins after surgery vs medical treatment, but many studies did show a corresponding reduction in medication usage.

Durability of the effects of surgery was demonstrated in a 5-year study that showed superior and durable weight loss and glycemic control (remission) with both RYGB and BPD in severely obese patients (BMI ≥ 35) vs medical therapy.32 Similarly, Schauer et al43 showed that RYGB and SG were more effective than intensive medical therapy in improving or, in some cases, resolving hyperglycemia for 5 years. In the RCTs, patients who preoperatively had shorter duration of diabetes, lower HbA1c levels, no insulin requirement, and more postoperative weight loss were more likely to achieve diabetes remission.

Although previous guidelines and payer coverage policies had limited metabolic surgery to severely obese patients (BMI ≥ 35 kg/m2), nearly all RCTs showed that the surgical procedures, especially RYGB and SG, were equally effective in patients with BMI 30 to 35 kg/m2. This is particularly important given that most patients with type 2 DM have a BMI less than 35 kg/m2. The effect of surgery in these patients with mild obesity is also durable out to at least 5 years.43

No RCT was sufficiently powered to detect differences in macrovascular or microvascular complications or death, especially at the relatively short follow-up, and no such differences have been detected thus far. The STAMPEDE (Surgical Therapy and Medications Potentially Eradicate Diabetes Efficiently) trial43 showed that bariatric surgery (RYGB or SG) did not appear to worsen or improve retinopathy outcomes at 5 years compared with intensive medical management.

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